Synthesis and characterization of novel bis – ( α – aminophosphonates ) with terminal chromone moieties

The 1,2,4,3,5-triazadiphosphinanyl derivative 5 and bis–(α–aminophosphonate) derivatives 6 and 8a,b bearing chromone moieties were synthesized by addition of diethyl phosphite to new condensation products that formed by condensation of 4-oxo-4H-chromene-3-carboxaldehyde (1) with phosphonic dihydrazide, 1,3-diaminopropane and 1,4-diaminobutane.


Scheme 1
Addition of diethyl phosphite to the azomethine bond of the hydrazone 2 required heating at 80-100 o C and triethylamine as a catalyst and gave 3-(4-amino-5-ethoxy-3,5-dioxido-1,2,4,3,5triazadiphosphinan-6-yl)-4H-chromen-4-one (5).Most likely, the addition leads to intermediate 4 (not isolated), which undergoes intramolecular cyclization via elimination of ethanol affording compound 5 (Scheme 2).The structure of compound 5 was established on the basis of elemental analysis and spectral data (IR, 1 H-, 13 C-and 31 P-NMR).The absorption bands at 1221, 1237 and 3084-3145 cm -1 observed in the IR spectrum were assigned to stretching frequencies of P=O, NH 2 and NH groups.The 1 H NMR spectrum showed the presence of one ethoxy group and a doublet at δ 3.95 ppm splitted by a H-P coupling of 24.5 Hz.The 13   Fusing of the bis-hydrazone 3 with diethyl phosphite at 80-100 o C in the presence of catalytic amounts of triethylamine produced N 1 ,N 5 -bis{N-methyl(diethoxyphosphonyl)-1-[(4-oxo-4Hchromen-3-yl)}phosphonic dihydrazide (6) as the sole product (Scheme 3).The structure was established by elemental analysis and the IR spectrum which showed absorption bands of NH and P=O groups at 3150 and 1214 cm -1 .The 1 H NMR spectrum of 6 revealed the presence of two ethoxy and CH-P groups.Accordingly, the 13 C NMR showed two signals at 45.46 and 51.32 ppm for CH-P of CH-P(O)(OEt) 2 groups.Moreover, the 31 P NMR showed triplet signal at δ 5.11 (t, J= 8.74 Hz) and singlet signal 21.75 ppm from the O=P-H and P(O)(OEt) 2 groups, respectively.Only one isomer was observed.
were prepared in moderate yield by condensation of aldehyde 1 with1,3-diaminopropane or 1,4-diaminobutane in dry benzene containing catalytic amounts of 4-toluenesulfonic acid (Scheme 4).The structures of the new bis-imines 7a,b were established using elemental analysis, IR, and 1 H NMR spectra (See Experimental Section).
The addition of diethyl phosphite to compounds 7a,b was carried out in dry benzene containing few drops of triethylamine as catalyst to yield the corresponding bis-(αaminophosphonates) derivatives 8a,b, respectively (Scheme 4).The IR spectra of 8a,b displayed absorptions at 1219-1218 (P=O) and 3116-3100 cm -1 (NH).The 1 H NMR spectra of compound 8a,b showed the presence of ethoxy groups.The 13  Scheme 4 The addition of diethyl phosphite to bis-imines 3 and 7a,b should lead to a mixture of the meso and racemic diasteromers. 16,17Each of the compounds 6 and 8a,b gave one spot by thin layer chromatography (TLC) and exhibited only one set of signals in the 1 H, 13 C and 31 P NMR spectra suggesting that only one diasteromer is formed.

Experimental Section
General Procedures.Melting points of the products were determined on a Kofler microscope and are uncorrected.The IR spectra were recorded on a Bruker IFS 1113 spectrophotometer in CDCl 3 solvent or KBr disks. 1 H NMR spectra (solvent DMSO-d 6 or CDCl 3 ) were recorded on a Bruker DRX (250 or 600 MHz) spectrometer using TMS as an internal standard. 13C and 31 P NMR spectra were registered on a Varian Inova 500 MHz spectrometer using TMS as an internal standard and 85% H 3 PO 4 as external reference, respectively.Thin layer chromatography (TLC) was performed on Kieselgel 60 F254 plastics sheets (Merck Sigma Chemical Co.Germany) applying the samples as solutions in CHCl 3 and eluting with benzene-methanol (10:1).4-Oxo-4H-chromene-3-carboxaldehyde (1) 18 and phosphonic dihydrazide 19 were prepared by the published methods.

15 ARKAT
C NMR showed signals from the CHP group as doublets.The 31 P NMR spectra of compounds 8a,b had singlet signals at δ 23.64 and 24.19 ppm, respectively, consistent with the presence of a phosphonate group.